Analysis of overall survival (OS) and progression-free survival (PFS) in the phase 1b clinical trial of anti–PD-1 ab (toripalimab) plus intrahepatic injection of orienX010 in stage IV melanoma with liver metastases.
Authors: Chuanliang Cui, Bin Lian, Yue Yang, Shanshan Yin, Yue Cong, Xuan Wang, Lu Si, Zhihong Chi, Xinan Sheng, Yan Kong, Lili Mao, Li Zhou, Bixia Tang, Xieqiao Yan, Xue Bai, Siming Li, Juan Li, Caili Li, Xiaoting Wei, Jun Guo
Journal: Journal of Clinical Oncology (2023)

9564 Background: Advanced melanoma with liver metastasis has a lower response rate and survival even in immunotherapy era which might because of its immunosuppressive tumor microenvironment. CPI combined with TVEC had showed a remarkable in cutaneous melanoma. The initial results of the phase 1b trial, systemic toripalimab (anti-programmed cell death-1 antibody) combined with Intratumoral injection of liver with OrienX010 - a HSV-1-derived oncolytic virotherapy with expression of GM-CSF in liver metastasis patients without extra-hepatic injectable lesions had shown its efficacy. Here we present the PFS and overall survival (OS) outcomes. Methods: Eligible pts included those over 18 with injectable liver metastasis confirmed by biopsy with or without extra-hepatic metastasis; the ocular melanoma and brain metastasis were excluded. Pts received intravenous toripalimab Q2W combined with ultrasound guided intratumoral injection of OrienX010 Q2W (8×10 7 pfu/ml, 10ml per injection) until intolerance or disease progression per iRECIST criteria. Liver biopsy would be performed at baseline and first tumor evaluation (8-12weeks). The primary endpoint was toxicity; secondary endpoints included ORR, disease control rate (DCR), PFS and OS. NCT04206358. Results: From Jul 2019 to Feb 2023, 30 pts enrolled. 60.0% pts primary from mucosal,; 73.3% got extra-hepatic metastasis; median size of injected lesions: 24mm(10-94mm); median number of liver metastasis: 7(1-10); median number of injection: 10 (3-36). Among these pts, 29 pts could be evaluated for efficacy. The median PFS was 7.0months (95%CI: 4.7-9.3 months) and the median OS was not reached. The 3-year OS rates 51.5%. The global ORR by investigator was 20.7% (6/29), DCR 48.3% (14/29); the response rate was 31.0%(9/29) for injected lesions, 30.0%(6/20) for non-injected lesions in liver, and 27.8% (5/18) for extra-hepatic metastases. For pts（21.7%( 2 PR and 3 SD)）with no melanoma cells residual by immunohistochemistry in biopsies the median PFS was 14.0 months (95%CI: 3.7-24.4 months), and it was much longer than that of other pts which was 4.1 months (95%CI: 1.4-6.8 months). The median OS of the pts with no melanoma cells was 19.7 months (95%CI: 7.5-31.9 months). Most adverse events (AE) were grade 1-2 and manageable. The grade 3-4 treatment-related AE included elevated transaminase (3 [10.0%]), nausea (1 [3.3%]), pulmonary embolism (1 [3.3%]) and vomiting (1 [3.3%]). No treatment-related deaths occurred. Conclusions: Systemic toripalimab combined with intrahepatic OrienX010 injection has shown remarkable long PFS, OS and ORR in melanoma pts with liver metastases with manageable toxicity. Clinical trial information: Clinical trial information: NCT04206358 .